STRUCTURE OF THE RECEPTORS FOR ORAL BACTERIAL ADHESINS

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Gingival inflammation is initiated by colonization of the mouth by flora dominated by streptococci and gram-positive rods which have been shown to coaggregate by the interaction of fimbrial lectins with polysaccharide receptors. The molecular basis of the interbacterial adherence leading to the formation of dental plaque and subsequent initiation of gingivitis and periodontal disease will be investigated. Studies will be carried out on the molecular structure of the microbial receptors responsible for species specific bacterial interactions which are required for colonization of the oral cavity. Existing data on the taxonomy, ecology, coaggregation properties and reactions with specific antibodies will be used to select representative strains of Streptococcus sanguis whose capsular polysaccharides are know to act as the receptors for the fimbrial lectins of Actinomyces species. The covalent chemical structure of the repeating subunit of the capsular polysaccharides of the selected strains will be determined. Oligosaccharide fragments from the repeating subunit isolated in the course of the structural studies will be available for use as probes of the immunological reactivity of bacterial antigens and as probes of the lectin receptor sites. The structures of the capsular polysaccharides of related Streptococcus sanguis strains will be correlated with the reactivity both with antibodies and with Actinomyces lectins in order to distinguish the immunodominant carbohydrate site and the site of the lectin receptor activity. The methodology to be used in the structure determination will emphasize high resolution nuclear magnetic resonance (NM) spectroscopy including complete assignments of the 1H and the 13C spectra and coupling correlation between 1H, 13C and 31P NM signals. The three dimensional conformation of the active sites of the polysaccharide will be determined from NM data, in particular 1H nuclear Overhauser enhancement (NOE), 1H-1H and 13C-1H vicinal coupling correlations in combination with computer molecular modeling.